Inability of donor total body irradiation to prolong survival of vascularized bone allografts: experimental study in the rat.
At the present time, the toxic side effects of recipient immunosuppression cannot be justified for human non-vital organ transplantation. Total body irradiation has proven effective in ablating various bone-marrow-derived and endothelial immunocompetent cellular populations, which are responsible for immune rejection against donor tissues. Irradiation at a dose of 10 Gy was given to donor rats six days prior to heterotopic transplantation of vascularized bone allografts to host animals. Another group of recipient rats also received a short-term (sixth to fourteenth day after grafting), low dose of cyclosporine. Total body irradiation was able merely to delay rejection of grafts across a strong histocompatibility barrier for one to two weeks, when compared to nonirradiated allografts. The combination of donor irradiation plus cyclosporine did not delay the immune response, and the rejection score was similar to that observed for control allografts. Consequently, allograft viability was quickly impaired, leading to irreversible bone damage. This study suggest that 10 Gy of donor total body irradiation delivered six days prior to grafting cannot circumvent the immune rejection in a vascularized allograft of bone across a strong histocompatibility barrier.
Gonzalez del Pino
J
J
Orthopaedic Research Laboratory, Johns Hopkins University School of Medicine, Baltimore, Maryland.
Benito
M
M
Randolph
M A
MA
Weiland
A J
AJ
D000818:Animals; D001853:Bone Marrow / Q000473:pathology; D016025:Bone Transplantation / Q000379:methods*; D003524:Cyclosporins / Q000627:therapeutic use; D005263:Femoral Artery / Q000473:pathology; D005268:Femoral Vein / Q000473:pathology; D006084:Graft Rejection / Q000187:drug effects / Q000528:radiation effects; D006085:Graft Survival / Q000187:drug effects / Q000528:radiation effects*; D006648:Histocompatibility; D007719:Knee Joint / Q000473:pathology / Q000601:surgery; D008297:Male; D011829:Radiation Dosage; D051381:Rats; D011917:Rats, Inbred Lew; D013997:Time Factors; D014019:Tissue Donors; D014654:Vascular Patency; D014916:Whole-Body Irradiation
D003524:Cyclosporins